Effectiveness of an Oral Gastrografin Regimen for Complete Distal Intestinal Obstruction Syndrome.

Objectives: To assess the effectiveness of oral Gastrografin treatment and outcomes in adult patients with complete distal intestinal obstruction syndrome (cDIOS). Background: DIOS is an important gastrointestinal complication of cystic fibrosis (CF). Conservative treatment options for cDIOS are largely empirical, and the optimal management remains unclear. Surgery should be reserved for patients who have failed nonoperative treatment or have immediate indications for surgery. Methods: A retrospective single-institution cohort study was undertaken of adults with CF who had undergone lung transplantation and were admitted with an episode of cDIOS between 2004 and 2020. The outcomes of treatment in a high-volume CF transplant center with routine oral Gastrografin-based therapy were assessed. Results: Forty-seven episodes of cDIOS were recorded in 29 (23.3%) of 124 patients who had undergone lung transplantation for CF, and mean age at cDIOS was 30.3 years (SD ±11.2). Mean follow-up post cDIOS was 75.6 months (SD ±45.5). Twelve patients had >1 cDIOS episode. One episode occurred during recovery after transplantation, and 5 patients were readmitted within 30 days posttransplant with cDIOS. A history of previous abdominal surgery was associated with the development of cDIOS (P < 0.001). Oral Gastrografin therapy was used in 95.7% of the episodes, at varying doses. Three patients (7.0%) were resistant to oral Gastrografin treatment, requiring laparotomy. There were no deaths due to DIOS. Conclusions: Oral Gastrografin is effective and safe for the treatment of cDIOS, with low treatment failure rates. It should be considered as a first-line treatment option for patients with CF presenting with complete distal intestinal obstruction.

Anal cancer: a 20-year retrospective study from Australia.

BACKGROUNDS: Anal cancer is an uncommon condition, occurring at higher rates in specific subpopulations. Clinical experience is limited and substantial changes have recently occurred in our understanding of this condition. We, therefore, set out to characterize patients presenting with anal cancer and investigate whether there have been any changes over the past 20 years. METHODS: Retrospective audit of cases identified from pathology and clinical databases during the period 1 January 2000 to 31 December 2019. RESULTS: Two hundred and sixteen patients had anal squamous cell carcinomas, comprising 160 (74%) males and 56 (26%) females. Mean age at initial diagnosis was 55.1 ± 11.20 for males and 60.6 ± 15.18 for females (P = 0.02). At initial diagnosis, HIV-positive cases were significantly younger than HIV negative cases (mean 52.2 ± 9.35 vs. 62.8 ± 11.61, P < 0.001); 46% of cases were classified as intra-anal, 29% perianal and 25% both; 52% were > 2 cm at diagnosis. At presentation, intra-anal cases were larger and more advanced than perianal cases (P = 0.049). Compared with the period 2000-2009, anal cancers presented more commonly in 2010-2019 (148 vs. 76), were more likely to occur in HIV-negative people and to be diagnosed at a similar stage. CONCLUSION: The number of anal cancer cases almost doubled over the study period and people living with HIV presented 10 years younger than others. Perianal cases presented earlier than those originating in intra-anal locations. Together with the large size at diagnosis, this suggests the potential value of screening, particularly for intra-anal cancers in those at high risk.

Should we inform women about the recognised risks of childbirth?

BACKGROUND: At present in Australia women are not routinely, systematically informed of the risks of childbirth. AIMS: It is hoped this presentation of the perspective of some women who suffer unexpected obstetric complications will encourage change. MATERIALS AND METHODS: The experience of women involved in obstetric medicolegal reports prepared by a colorectal surgeon over ten years is analysed. RESULTS: Twenty women were identified. Sixteen had vaginal deliveries. All 16 suffered third or fourth-degree tears, six developed rectovaginal fistulae, six required stomas and 11 developed faecal incontinence. Of the four women who delivered by caesarean section, there were two post-operative caecal perforations, one unrecognised small bowel enterotomy, and one patient developed sepsis due to an infected haematoma. Seventeen of the 20 women were noted to suffer psychological sequalae. None of the women recollected being warned of the complication they suffered, and there was no record of such warnings in their medical records. CONCLUSION: Informed written 'consent' for natural vaginal delivery is, understandably, a contentious topic. Although learning from medicolegal cases may go against the grain, as medical professionals it is very difficult to ethically justify the status quo, where women are not routinely simply informed of the risks of childbirth. This is not fair. Even if informing women does not decrease the incidence of complications, the women who subsequently suffer these complications may well handle them much better, recognising they could occur.

Abdominal wall closure with prophylactic mesh in colorectal operations.

BACKGROUND: Prospective studies demonstrate that over one-third of patients undergoing standard suture closure of laparotomy wounds will develop incisional hernias (IHs). Whilst prophylactic mesh has been demonstrated to decrease IH rates in clean laparotomy wounds, mesh has been associated with high rates of seroma formation (>30%), infection (>10%) and pain, discouraging many surgeons from using mesh, especially combined with intestinal surgery. The aim of this study is to review the experience of a single colorectal surgeon who, after noting high IH rates in his own patients, started placing prophylactic mesh routinely in patients judged to be at high risk of IH. METHODS: The records of all patients undergoing bowel resections and ileostomy closure by one surgeon from 2008 to 2018 were independently retrospectively analysed. RESULTS: Of the 935 procedures identified, 662 patients underwent midline laparotomy with bowel resection and 273 patients underwent closure of loop ileostomy. Mesh was placed prophylactically in 221 (23.6%) of 935 procedures. Comparing the mesh and non-mesh groups, wound infections occurred in nine (4.1%) versus 23 (3.2%) (P = 0.53), seromas occurred in nine (4.1%) versus six (0.8%) (P = 0.003) and chronic pain was noted in 12 (5.4%) versus 17 (2.4%) (P = 0.04). The mean follow-up was 33 months in both the mesh and non-mesh groups. IHs have occurred in three (1.3%) of the mesh group compared to 95 (13.3%) of the non-mesh group procedures (P = 0.0001). CONCLUSION: In colorectal operations, prophylactic mesh decreases the risk of IH without prohibitive complications.

Circumferentially oversewn inverted stapled anastomosis.

BACKGROUND: Leak rates of over 5% following anastomoses between the ileum and colon continue to be reported in large series and are associated with substantial morbidity and with mortality rates of 10-20%. In 1994, we began performing circumferentially oversewn inverted stapled anastomoses in patients undergoing ileo-colic anastomoses or ileostomy closure. It has become increasingly apparent that this method is associated with a low risk of leakage, which we should report. METHODS: The anastomotic technique described was used in all patients undergoing ileo-colic anastomosis or closure of ileostomy by surgeon 1 (1994-2015) and in all ileo-colic anastomoses by surgeon 2 (2007-2015). All patients had a widely patent anastomosis constructed by two firings of a linear cutting stapler, as previously described. Additionally, the entire staple line was carefully oversewn with interrupted, inverting 4/0 polydioxanone sutures. Anastomotic leak was defined as a patient requiring re-operation or radiological drainage. RESULTS: One thousand and twelve patients underwent ileo-colic anastomosis and 685 patients underwent closure of ileostomy by surgeon 1, and 165 patients underwent ileo-colic anastomosis by surgeon 2. None of the 1862 patients required re-operation or radiological drainage for a leak (event rate 0%, 95% confidence interval 0-0.2%). However, there were three possible contained leaks treated successfully conservatively. The time taken to perform the actual anastomosis was measured in the last 30 ileo-colic resections. The median time was 42 min. CONCLUSION: While this method may well be too slow to gain widespread adoption, we hope this report encourages increased research into finding techniques with similar low leak rates.

Is it right to ignore learning-curve patients? Laparoscopic colorectal trials.

BACKGROUND: Increasingly complex, technically demanding surgical procedures utilizing emerging technologies have developed over recent decades and are recognized as having long 'learning curves'. This raises significant new issues. Ethically and scientifically, the outcome of a patient in the learning curve is as important as the outcome of a patient outside the learning curve. The aim of this study is to highlight just one aspect of our approach to learning-curve patients that should change. METHODS: The protocols of multicentre, prospective, randomized trials of patients undergoing either traditional open or laparoscopic surgery for colorectal cancer were reviewed. The number of patients excluded from the published trial results because they were in surgeons' learning curves was calculated. The seven editorials accompanying these publications were also examined for any mention of these patients. RESULTS: The eight studies identified had similar designs. All patients in the surgeons' laparoscopic learning curves, which were often several years long, were excluded from the actual trials. The total number of patients included in the trial publications was 5680. The number of patients excluded because they were in the surgeons' laparoscopic learning curves was >10 605. In none of the studies or accompanying editorials is there any mention of the total number of patients in the surgeons' learning curves, these patients' outcomes or how inclusion of their outcomes might have affected the overall results. CONCLUSION: Learning curves are inescapable in modern medicine. Our recognition of patients in these curves should evolve, with more data about them included in trial publications.

Multicenter randomized trial of centralized nurse-led telephone-based care coordination to improve outcomes after surgical resection for colorectal cancer: the CONNECT intervention.

PURPOSE: To investigate the effectiveness of a centralized, nurse-delivered telephone-based service to improve care coordination and patient-reported outcomes after surgery for colorectal cancer. PATIENTS AND METHODS: Patients with a newly diagnosed colorectal cancer were randomly assigned to the CONNECT intervention or usual care. Intervention-group patients received standardized calls from the centrally based nurse 3 and 10 days and 1, 3, and 6 months after discharge from hospital. Unmet supportive care needs, experience of care coordination, unplanned readmissions, emergency department presentations, distress, and quality of life (QOL) were assessed by questionnaire at 1, 3, and 6 months. RESULTS: Of 775 patients treated at 23 public and private hospitals in Australia, 387 were randomly assigned to the intervention group and 369 to the control group. There were no significant differences between groups in unmet supportive care needs, but these were consistently low in both groups at both follow-up time points. There were no differences between the groups in emergency department presentations (10.8% v 13.8%; P = .2) or unplanned hospital readmissions (8.6% v 10.5%; P = .4) at 1 month. By 6 months, 25.6% of intervention-group patients had reported an unplanned readmission compared with 27.9% of controls (P = .5). There were no significant differences in experience of care coordination, distress, or QOL between groups at any follow-up time point. CONCLUSION: This trial failed to demonstrate substantial benefit of a centralized system to provide standardized, telephone follow-up for postoperative patients with colorectal cancer. Future interventions could investigate a more tailored approach.

Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa.

Folate exists as functionally diverse species within cells. Although folate deficiency may contribute to DNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P < 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy individuals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same individual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to individual cells rather than the entire colon.

Quantitative analysis of tissue folate using ultra high-performance liquid chromatography tandem mass spectrometry.

The tissue distribution of folate in its numerous coenzyme forms may influence the development of disease at different sites. For instance, the susceptibility of human colonic mucosa to localized folate deficiency may predispose to the development of colorectal cancer. We report a sensitive and robust ultra high-performance liquid chromatography (UHPLC) tandem mass spectrometry method for quantifying tissue H(4)folate, 5-CH(3)-H(4)folate, 5-CHO-H(4)folate, folic acid, and 5,10-CH(+)-H(4)folate concentration. Human colonic mucosa (20-100mg) was extracted using lipase and conjugase enzyme digestion. Rapid separation of analytes was achieved on a UHPLC 1.9-µm C18 column over 7 min. Accurate quantitation was performed using stable isotopically labeled ((13)C(5)) internal standards. The instrument response was linear over physiological concentrations of tissue folate (R(2)>0.99). Limits of detection and quantitation were less than 20 and 30 fmol on column, respectively, and within- and between-run imprecision values were 6-16%. In colonic mucosal samples from 73 individuals, the average molar distribution of folate coenzymes was 58% 5-CH(3)-H(4)folate, 20% H(4)folate, 18% formyl-H(4)folate (sum of 5-CHO-H(4)folate and 5,10-CH(+)-H(4)folate), and 4% folic acid. This assay would be useful in characterizing folate distribution in human and animal tissues as well as the role of deregulated folate homeostasis on disease pathogenesis.

Distal intestinal obstruction syndrome (DIOS) in patients with cystic fibrosis after lung transplantation.

BACKGROUND: Cystic fibrosis (CF) is the commonest inherited life-threatening disease in Caucasians. With increased longevity, more patients with CF are developing gastrointestinal complications including the distal intestinal obstruction syndrome (DIOS), in which ileocecal obstruction is caused by viscid mucofeculent material. The optimal management of DIOS is uncertain. METHODS: The medical records of all patients with CF who underwent lung transplantation at this institution during a 15-year period were reviewed. The definition of DIOS required the presence of both clinical and radiological features of ileocecal obstruction. RESULTS: One hundred twenty-one patients with CF underwent lung transplantation during the study period. During a minimum 2-year follow-up, there were 17 episodes of DIOS in 13 (10.7%) patients. The development of DIOS was significantly associated with a past history of meconium ileus (odds ratio 20.7, 95% C.I. 5.09-83.9) or previous laparotomy (odds ratio 4.93, 95% C.I. 1.47-16.6). All six patients who developed DIOS during the transplantation admission had meconium ileus during infancy, and five had undergone pretransplant laparotomy for CF complications. First-line treatment for all patients was a combination of medication (laxatives, stool softeners, and bowel preparation formulas). This was successful in 14 of the 17 DIOS but needed to be given for up to 14 days. The other three patients required laparotomy with enterotomy and fecal disimpaction. This provided definitive resolution of DIOS except in one patient who presented late and died despite ileal decompression and ileostomy. CONCLUSIONS: DIOS occurred in approximately 10% of CF patients after lung transplantation. Patients with a history of meconium ileus or previous laparotomy are at high risk of developing DIOS. Patients with DIOS require early aggressive management with timely laparotomy with enterotomy and possible stoma formation when non-operative therapy is unsuccessful.

Multimedia article. An improved technique for end stoma creation in obese patients.

PURPOSE: The formation of an end colostomy in obese patients can be technically demanding and often requires the creation of a particularly large defect in the abdominal wall. This is because of the thickness of the subcutaneous fat and mesenteric fat, and increased resistance or friction while negotiating the bowel and mesentry through the abdominal wall. METHODS: The use of an Alexis Wound Protector to circumferentially retract the abdominal wall defect and, thus decrease resistance or friction during stoma formation, is described (see Video, Supplemental Digital Content 1 and 2, which demonstrates the technique, http://links.lww.com/A997 and http://links.lww.com/A998). RESULTS: This technique has been used in eight obese patients who have undergone end stoma formation. In each patient, the efficacy of the wound protector was immediately obvious, resulting in a smaller than usual defect in the abdominal wall and less trauma to the bowel. CONCLUSIONS: The use of a wound protector has decreased the size of the abdominal wall defect necessary for stoma creation in obese patients and hopefully will decrease the risk and rate of parastomal hernia formation.

Severe diverticulitis after heart, lung, and heart-lung transplantation.

BACKGROUND: In this study, we reviewed our experience with severe diverticulitis in patients who have undergone heart and/or lung transplantation to assess whether transplant recipients are at increased risk of having severe diverticulitis compared with the general population. METHODS: We reviewed the records of patients who underwent heart and/or lung transplantation from 1984 to 2000, inclusive, and identified patients with severe diverticulitis that required surgery or that resulted in death. We compared this incidence with the incidence of such complications in the general population, served by the same institution during a 2-year period, 1999 to 2000. RESULTS: A total of 953 patients underwent transplantation in the study period. The mean follow-up was 57 months, a total follow-up of 4528 patient-years. Nine patients (mean age, 54 years) had severe diverticulitis that required surgical intervention (8 patients) or that resulted in death (1 patient died without surgical intervention). During 1999 to 2000, 16 patients (mean age, 66 years) from the general population were treated for severe diverticulitis that required surgical intervention, 3 of whom died. From census and area health data, we found that the study institution serves approximately 90000 people older than 40 years, with a total follow-up of 180000 patient-years. The incidence rate ratio for severe diverticulitis when comparing the transplant with the non-transplant groups was 22.2 (95% confidence interval; 9.9-50.0; p < 0.001). CONCLUSIONS: Patients with severe diverticulitis who have undergone heart and/or lung transplantation can be treated surgically with a small mortality rate. Transplant recipients probably are at substantially increased risk of experiencing severe diverticulitis.

Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer.

BACKGROUND AND OBJECTIVES: Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16(INK4a) gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p16 expression and its relationship to hypermethylation in sporadic colorectal cancer. METHODS: Tissue from 426 colorectal cancers underwent histological analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA was analyzed for microsatellite instability (MSI) and the presence of K-ras mutations. In addition, DNA was bisulphite-modified and analyzed for p16(INK4a) promoter methylation by methylation-specific PCR. RESULTS: There were 25% of tumors with p16(INK4a) promoter hypermethylation. These tumors were associated with older patients, right-sidedness, MSI and were poorly differentiated, mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's-type lymphocytic reaction (P < 0.05). However, only right-sidedness was significant on multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and this was associated with hypermethylation (P < 0.05). CONCLUSION: p16(INK4a) promoter methylation, although common in colorectal cancer, does not result in a clinicopathologically distinct subgroup of tumors and infrequently results in transcriptional silencing. This suggests that p16(INK4a) gene inactivation does not have an important role in the pathogenesis of sporadic colorectal cancer.

Histopathological and clinical evaluation of serrated adenomas of the colon and rectum.

We evaluated the diagnostic utility of the histological characteristics ascribed in the literature to serrated adenomas and developed a practical working model to allow their reliable identification. We also documented the frequency and location of serrated adenomas identified in an unselected series of individuals undergoing colonoscopic evaluation, as well as the clinical characteristics of those individuals. One hundred forty consecutive individuals (prospective polyp data set; 97 male, 43 female; age mean: 63.3 y; age range: 29-98 y) with 255 polyps were identified from 919 individuals undergoing colonoscopy. Further polyps previously removed from these individuals were added for the purpose of histological assessment (extended polyp data set, n = 380). All polyps were assessed by two independent examiners for eight selected architectural and cytological features of serrated adenomas. In the prospective polyp data set, 56 patients had 72 hyperplastic polyps, 7 had 9 serrated adenomas, 3 had 4 admixed polyps, and 98 had 170 conventional adenomas. There was no difference in the age, sex, or cancer association of the seven patients with serrated adenomas when compared with the case of other individuals with polyps. The prevalence of serrated adenomas was 9/919 (1%) in our population, with an average size of 5.8 mm. When assessing serrated adenomas histologically, the combination of nuclear dysplasia and serration of >/=20% of crypts provided the most accurate model for detection of these lesions (sensitivity 100%, specificity 97%). Other criteria provided supportive evidence but did not increase the diagnostic yield. The optimum model for the histological identification of the serrated adenoma includes the presence of a serrated architecture in >/=20% of crypts in association with surface epithelial dysplasia.

Current evidence does not support routine adjuvant radiotherapy for rectal cancer.

BACKGROUND: There is widespread support in the published literature for routine adjuvant radiotherapy for rectal cancer. METHODS: In the present paper, the current evidence regarding adjuvant radiotherapy is reviewed, particularly the most recent studies of preoperative radiotherapy (usually including patients with Stage I, II and III disease) and postoperative radiotherapy (usually for Stage II and III disease), and meta-analyses. Two questions in particular are addressed: Does radiotherapy improve survival when surgeons are able to achieve low local recurrence rates with surgery alone? Does radiotherapy improve patients' quality of life? RESULTS: Radiotherapy has only been demonstrated to significantly improve survival in one individual study and one recent meta-analysis. The local recurrence rates in the no-radiotherapy arm of these studies were 27% and 21-36.5%, respectively. In more recent studies, with lower local recurrence rates reflecting modern surgical standards, no survival advantage has been found. It is currently unknown whether radiotherapy improves patients' quality of life. Studies have demonstrated that radiotherapy has acute and long-term detrimental effects on quality of life. While local recurrence can be very debilitating, it can also be asymptomatic, and the overall effect of the local recurrence statistics found in adjuvant therapy studies on quality of life has not been systematically investigated. The most recent studies demonstrate that 17-20 patients need to undergo adjuvant radiotherapy to prevent one local recurrence. CONCLUSION: Current evidence does not support the widespread advocacy for routine adjuvant radiotherapy as used in the treatment arms of recent trials.

The role of hMLH1 methylation in the development of synchronous sporadic colorectal carcinomas.

PURPOSE: AB. B. subset of sporadic colorectal carcinomas show microsatellite instability, usually as a result of biallelic hMLH1 gene promoter methylation. Synchronous tumors occur in up to 5 percent of patients with colorectal cancer, but their cause is poorly understood. We hypothesized that in the setting of sporadic microsatellite instability cancers, synchronicity may reflect a global predisposition of colorectal epithelium toward tumor development because of gene hypermethylation. METHODS: We identified 14 individuals with 33 synchronous cancers from a series of 362 patients with 381 sporadic colorectal cancers. We then analyzed the synchronous lesions for microsatellite status, hMLH1 protein expression, and hMLH1 promoter methylation. RESULTS: Seven of 33 synchronous tumors (21 percent) showed microsatellite instability, compared with 36 of 348 solitary tumors (10.3 percent, P = 0.06). The 14 patients with synchronous tumors were significantly older than those with solitary tumors (mean age 79.4 vs. 68.2 years, P = 0.01), and 5 of these patients had at least one microsatellite instability tumor. However, only one patient harbored synchronous tumors that were all of the microsatellite instability type. Methylation of the hMLH1 promoter was seen in 9 synchronous cancers from 27 assessable lesions in 7 patients and was associated with microsatellite instability (P = 0.01), right-sidedness (P = 0.01), and loss of expression of hMLH1 (P = 0.03). Only one case showed methylation in all synchronous tumors, whereas in five cases synchronous tumors showed different methylation status within the one individual. CONCLUSION: Our data suggest that synchronous tumors arise as independent events and that the slightly greater frequency of synchronous tumors in individuals with microsatellite instability cancers is likely to be a chance event reflecting the older age of these individuals rather than arising from a predisposition toward cancer as a result of global hypermethylation of colorectal epithelium.

Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease.

BACKGROUND AND AIM: Thalidomide is clinically effective in the treatment of graft versus host disease in bone marrow transplantation and aphthous ulceration in HIV infection. It appears to exert a selective effect on tumor necrosis factor-alpha (TNF-alpha) production. Tumor necrosis factor-alpha is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy and safety of thalidomide in symptomatic IBD. METHODS: Eleven patients (nine males, mean age 33 years, range 20-77 years) with chronic inflammatory bowel disease (six Crohn's disease (CD), four ulcerative colitis (UC), one indeterminate colitis (IC)) who were symptomatic despite standard medical therapy were administered a daily dose of thalidomide for 12 weeks in an open-labeled protocol. Their response was assessed by using clinical, colonoscopic, histological, and immunological methods. RESULTS: Two patients withdrew at 3 weeks because of mood disturbances. Of the remaining nine patients, eight (five CD, two UC and one IC) had a marked clinical response, while one patient with CD had no response. The mean stool frequency decreased from 4.3 to 2.3 per day (P = 0.0012), and the stool consistency increased from 2.1 to 1.2 (P = 0.02). The mean Crohn's Disease Activity Index decreased from 117 to 48 (P = 0.0008). Endoscopic inflammatory and histological grade, C-reactive protein and erythrocyte sedimentation rate (ESR) all decreased significantly (P = 0.011, P = 0.03, P = 0.023 and P = 0.044, respectively). However, the serum TNF-alpha levels did not change. Side-effects included mild sedation, xerostomia and skin dryness in all, constipation in three, and minor abnormalities in nerve conduction in one patient. CONCLUSION: These data strongly suggest that thalidomide is an effective short-term treatment for symptomatic IBD.